DESCRIPTION: The B5R protein encoded by vaccinia virus appears to be a multifunctional protein which affects viral pathogenesis as well as the formation of the extracellular enveloped (EEV) forms of the virus. Mutants lacking B5R are defective in forming EEV (10-fold decrease), form small plaques in culture, and are attenuated in vivo. The extracellular domain of B5R, which appears not to be essential for EEV formation, contains SCR repeats that are homologous to a family of proteins involved in complement control. The goals of this proposal are to: (1) Define the domains of B5R that are essential for EEV formation; (2) determine the functional significance of the various B5R domains in pathogenesis in vivo; (3) anallyze the complement regulatory properties of B5R. Finally, if the ectodomain of B5R is not important for EEV formation, replacement of this domain with other proteins might permit targeting of EEV to specific cells or organs. Overall, the proposal is aimed at understanding the contribution of B5R to viral dissemination and pathogenesis with the hope that this understanding will enable the construction of safer recombinant vaccines.